Hypereosinophilic Syndrome
Conditions
Keywords
Mepolizumab, Open-label, Anti-IL-5, Hypereosinophilic Syndrome, Hypereosinophilia
Brief summary
This is an open label study of mepolizumab 750 mg intravenous in those subjects who participated in study 100185 to evaluate the long term safety and efficacy of mepolizumab in subjects with hypereosinophilic syndrome. The study will also evaluate the optimal dosing frequency for clinical use, the effects on corticosteroid reduction, and decrease of signs and symptoms of Hypereosinophilic Syndrome.
Interventions
DRUGmepolizumab
Study Drug
Sponsors
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Signed informed consent. * Subjects who have participated in Study MHE100185 and have been administered at least 2 doses of study medication. * Not pregnant or nursing * Of non-childbearing potential (i.e., women who had a hysterectomy, are post-menopausal which is defined as 1 year without menses, have both ovaries surgically removed, or have current documented tubule ligation); or * Of childbearing potential (i.e., women with functional ovaries and no documented impairment of oviductal or uterine function that would cause sterility). This category includes women with oligomenorrhoea \[even severe\], women who are perimenopausal or have just begun to menstruate. These women must have a negative serum pregnancy test at the Screening Visit, and agree to one of the following:1). Complete abstinence from intercourse from 2 weeks prior to administration of the first dose of investigational product until 3 months after the last dose of investigational product; Or 2). Consistent and correct use of one of the following acceptable methods of birth control for one month prior to the start of the investigation product and three months after the last dose:Male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for the female subjects; Implants of levonorgestrel;Injectable progestogen;Any intrauterine device (IUD) with a documented failure rate of less than 1% per year; Oral contraceptives (either combined or progestogen only)
Exclusion criteria
* Has developed life-threatening or other serious illness or clinical manifestation deemed inappropriate for inclusion in study per the principal investigator * Has any of the following abnormal laboratory values at the Week36/EW Visit of Study MHE100185: • Serum creatinine ≥3 times institutional upper limit normal (ULN); • AST or/ALT ≥5 times institutional ULN; • Platelet count \< 50,000/uL * Has developed abnormal cardiac functions, as the following, within past 3 months:• Left ventricular ejection fraction (LVEF) \< 20%; • NYHA class IIIb or IV; • Angina or acute myocardial infarction * Has developed allergic reaction to Study MHE100185 investigational product Use of an investigational drug as concurrent medication * Does not complete Week36/EW Visit assessments required in Study MHE100185 * Has completed or been terminated from Study MHE100185 for more than 1 month * Recent history or suspicion of current drug abuse or alcohol abuse within the last 6 months * Positive pregnancy test at the Week36/EW Visit of Study MHE100185
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Any Adverse Event (AE) During the Treatment Phase | From the first dose of study medication up to 7 days after the last dose (up to approximately 6 years) | An AE is any untoward medical occurrence in clinical investigation participants temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs are summarized by Treatment phase. Safety and tolerability of the study drug was assessed by number of participants with any AE |
| Number of Participants With Any Adverse Event (AE) During the Follow-up Phase | From end of Treatment Phase up to 97 days after the last dose date (up to approximately 6 years) | An AE is any untoward medical occurrence in clinical investigation participants temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs are summarized by Follow-up phase. Safety and tolerability of the study drug was assessed by number of participants with any AE |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| For Those Participants Who Completed 9 Months of Dosing in Study MHE100185 and Achieved a Prednisone Level <=10 mg: Number of Participants Achieving <= 10 mg Prednisone (as Sole Background Therapy) for >= 3months | up to approximately 6 years | Participants from study MHE100185 who completed the 9 months treatment period and achieved a level of \<=10 mg of prednisone at study end were analyzed. Duration of doses \<=10 mg was determined by examining changes in the prednisone dosing or allowable alternative corticosteroid medication (prednisone equivalents). Start and stop dates of other HES medications were checked to ensure that they did not overlap with the steroid dosing dates. If it did, then the number of days \<=10 mg during this overlap was considered as zero and the cumulative days reset to zero, as the endpoint was assessing prednisone dose as sole background therapy. The dosing criteria for this endpoint was considered as achieved if the duration of dosing was minimum of 84 days (3months). |
| For Those Participants Who Completed 9 Months of Dosing in Study MHE100185 and Achieved a Prednisone Level >10 mg: Number of Participants Achieving <=10 mg Prednisone (as Sole Background Therapy) for >= 8 Weeks | up to approximately 6 years | Participants from study MHE100185 who completed the 9 months treatment period and achieved a level of prednisone of \>10 mg at the end of the study were analyzed. Duration of doses \<= 10 mg were determined by examining changes in the prednisone dosing or allowable alternative corticosteroid medication (prednisone equivalents). Start and stop dates of other HES medications were checked to ensure that they did not overlap with the steroid dosing dates. If overap occurred, then the number of days \<=10 mg during this overlap was considered as zero and the cumulative days reset to zero, as the endpoint was assessing prednisone dose as sole background therapy. The dosing criteria for this endpoint was considered as achieved if the duration of dosing was minimum of 53 days (8 weeks). |
| For Those Participants Who Entered Stage 2 From Study MHE100185 With a Prednisone Level of <=10 mg Prednisone: Number of Participants Achieving a Prednisone Dose <=10 mg (as Sole Background Therapy) for >=3 Months; | up to approximately 6 years | Participants from study MHE100185 who completed the 9 months treatment period and achieved a level of \<=10 mg of prednisone at study end and participants who withdrew from the study early who were at a prednisone dose level \<=10 mg were analyzed. Duration of doses \<= 10 mg were determined by examining changes in the prednisone dosing or allowable alternative corticosteroid medication (prednisone equivalents). Start and stop dates of other HES medications were checked to ensure that they did not overlap with the steroid dosing dates. If overlap occurred, then the number of days \<=10 mg during this overlap was considered as zero and the cumulative days reset to zero, as the endpoint was assessing prednisone dose as sole background therapy. The dosing criteria for this endpoint was considered as achieved if the duration of dosing was minimum of 84 days (3months). |
| For Those Participants Who Entered Stage 1 From Study MHE100185 With >10 mg Prednisone: Number of Participants Achieving a Prednisone Dose <=10 mg (as Sole Background Therapy) for>=3 Months | up to approximately 6 years | Participants from study MHE100185 who completed the 9 months treatment period and achieved a level of \>10 mg prednisone at the end of the study and participants who withdrew from the study early who were at a prednisone dose level \>10 mg were analyzed. Duration of doses \<= 10 mg was determined by examining changes in the prednisone dosing or allowable alternative corticosteroid medication (prednisone equivalents). Start and stop dates of other HES medications were checked to ensure that they do not overlap with the steroid dosing dates. If it did, then the number of days \<=10 mg during this overlap was considered as zero and the cumulative days reset to zero, as the endpoint was assessing prednisone dose as sole background therapy. The dosing criteria for this endpoint was considered as achieved if the duration of dosing was minimum of 84 days (3months) |
| Blood Eosinophil Count (With Consideration of the HES Background Therapy) During Stages 1-3 | up to approximately 6 years | Mean blood eosinophil counts were summarized over time taking into account the effect of HES background therapy. Eosinophil count observations for only those participants taking mepolizumab in conjunction with prednisone or as monotherapy were included. |
| Number of Participants Achieving a Prednisone Level of =<10 mg (as Sole Background Therapy) at the End of Study | up to approximately 6 years | Participants who were receiving a prednisone dose level of =\<10 mg as their sole background therapy at the end of the study were included for the analysis. |
| Change From Baseline in the Pruritus Visual Analogue Scale (pVAS) 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Baseline and up to approximately 6 years | The pruritus visual analogue scale asks participants to rate the status of their Pruritus based on the severity of their itch. Scores range from 0-100 with 0 = No itch and 100 = Worst imaginable itch. Change from Baseline in pVAS score is the difference between the pVAS score at the time point being considered to the MHE100901 Baseline score. |
| Change From Baseline in Erythema/Edema Score 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Baseline and up to approximately 6 years | The erythema subscale score and edema subscale score are each graded on a 0-3 scale, with 0 = absent , 1 = mild, 2 = moderate, 3 = severe. The total score ranged from 0 to 6, with higher scores indicative of more severe Erythema/Edema. The total score was obtained by summing together the responses for each of the two subscale items. Change from Baseline in erythema/edema total score is the difference between erythema/edema total score at the time point being analyzed to the MHE100901 Baseline score.. |
| Change From Baseline in Quality of Life (QoL) and Current Health Status: Physical Summary Score of the Study Short Form Health Survey (SF-12) 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Baseline and up to approximately 6 years | The SF-12v2 is the 12 item abbreviated form of SF-36v2 survey . It provides information about how participants feel, and how well they have been able to perform their usual activities, over the past 4 weeks. SF-12v2 questions make up 8 scales: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, Mental Health . Transformed physical component summary score (PCS-12) is derived using all the 12 items and scored onto a 0-100 scale such that a higher score indicates a better health state and better functioning. Change from Baseline in scale or summary measure score is the difference between the score at the time point being analyzed to Baseline. |
| Change From Baseline in QoL and Current Health Status: Mental Summary Score of the SF12 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Baseline and up to approximately 6 years | The SF-12v2 is the 12 item abbreviated form of SF-36v2 survey developed by the Medical Outcomes Trust and QualityMetric Incorporated. It provides information about how participants feel, and how well they have been able to perform their usual activities, over the past 4 weeks. SF-12v2 scale questions make up 8 scales: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, Mental Health are for mental component summary. Transformed mental component summary score (MCS-12) is derived using all the 12 items and scored onto a 0-100 scale such that a higher score indicates a better health state and better functioning. Change from Baseline in scale or summary measure score is the difference between the score at the time point being analyzed to Baseline. |
| Number of Participants by Dosing Frequency Groups (Defined as Two Week Dosing Ranges Greater Than a 4 Week Interval) at the End of Stage 2 | up to approximately 6 years | The number of participants at the end of Stage 2 with study medication dosing frequencies of 4 weeks, 5-6 weeks, 7-8 weeks, 9-10 weeks, 11-12 weeks, 13-16 weeks, 17-20 weeks, 21-24 weeks and \>24 weeks were summarized. The first infusion date in Stage 3 and the last infusion date in Stage 2 were used to calculate the dosing frequency. |
| Number of Participants Achieving an Eosinophil Level of < 600 Cell/Microliter (uL) (in Addition to the Lowest Background Therapy) at the End of Study | up to approximately 6 years | The criteria for eosinophil count was achieved if the participant's eosinophil count remained below \<600 cell/uL for the last observation on study i.e. within length of dosing cycle + 7 days of last dose of study drug. For participants who entered in Stage 1, HES medications taking prior to the first infusion date in Stage 2 were considered as the lowest background therapy. For participants who entered in Stage 2, HES medications taken on the date that immediately preceded the first infusion date of study drug and had not been discontinued was regarded as the lowest background therapy. If the dose of the lowest background therapy had increased or the medication had changed or the participant had not reached their lowest background therapy, the participant was regarded as not achieving this endpoint. |
Countries
Australia, Belgium, Canada, France, Germany, Italy, United States
Participant flow
Recruitment details
Participants (par.) who completed 9 months of treatment or withdrew from Study MHE100185 after receiving \>=2 infusions of study medication were enrolled in this open label extension study. Par. with daily dose of prednisone \>10 milligrams (mg) or \<=10 mg at the end of Study MHE100185 were enrolled in Stage 1 or Stage 2 of this study, respectively.
Pre-assignment details
This study was open-label extension to previous Study MHE100185 (NCT00086658). A total of seventy-eight participants participated in this study. Of these, 38 participants previously received placebo in Study MHE100185 and 40 participants previously received mepolizumab in Study MHE100185.
Participants by arm
| Arm | Count |
|---|---|
| Mepolizumab 750 mg Participants received mepolizumab 750 mg by IV infusion monthly in Stage 1 along with concomitant HES-active medications that included prednisone (or equivalent) or other HES therapies. In Stage 2, the dosing intervals were optimized for each participant based on the individual's blood eosinophil count and the clinical presentation. In Stage 3, the dosing frequency established in Stage 2 was continued with individual participant monitoring. | 78 |
| Total | 78 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Stage 1 | Adverse Event | 3 |
| Stage 1 | Lack of Efficacy | 2 |
| Stage 1 | Withdrawal by Subject | 1 |
| Stage 2 | Adverse Event | 5 |
| Stage 2 | Lack of Efficacy | 3 |
| Stage 2 | Lost to Follow-up | 1 |
| Stage 2 | Pregnancy | 1 |
| Stage 2 | Sponsor Terminated Study | 2 |
| Stage 2 | Withdrawal by Subject | 1 |
| Stage 3 | Adverse Event | 2 |
| Stage 3 | Lack of Efficacy | 1 |
| Stage 3 | Lost to Follow-up | 1 |
| Stage 3 | Sponsor Terminated Study | 52 |
| Stage 3 | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Mepolizumab 750 mg |
|---|---|
| Age, Continuous | 49.2 Years STANDARD_DEVIATION 14.89 |
| Race/Ethnicity, Customized Arabic/North African | 2 Participants |
| Race/Ethnicity, Customized Black | 6 Participants |
| Race/Ethnicity, Customized East and South East Asian | 2 Participants |
| Race/Ethnicity, Customized South Asian | 1 Participants |
| Race/Ethnicity, Customized White/Caucasian | 67 Participants |
| Sex: Female, Male Female | 36 Participants |
| Sex: Female, Male Male | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 72 / 78 |
| serious Total, serious adverse events | 40 / 78 |
Outcome results
Primary
Number of Participants With Any Adverse Event (AE) During the Follow-up Phase
An AE is any untoward medical occurrence in clinical investigation participants temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs are summarized by Follow-up phase. Safety and tolerability of the study drug was assessed by number of participants with any AE
Time frame: From end of Treatment Phase up to 97 days after the last dose date (up to approximately 6 years)
Population: Follow-up Population: subset of the modified ITT Population who had evidence of being in the study \> length of dosing cycle + 7 days after the date of their last dose of study medication and up to and including 97 days after their last dose date.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mepolizumab 750 mg | Number of Participants With Any Adverse Event (AE) During the Follow-up Phase | 3 Participants |
Primary
Number of Participants With Any Adverse Event (AE) During the Treatment Phase
An AE is any untoward medical occurrence in clinical investigation participants temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs are summarized by Treatment phase. Safety and tolerability of the study drug was assessed by number of participants with any AE
Time frame: From the first dose of study medication up to 7 days after the last dose (up to approximately 6 years)
Population: Intent-to-Treat (ITT) Population: all enrolled participants who received at least one dose of mepolizumab in this study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mepolizumab 750 mg | Number of Participants With Any Adverse Event (AE) During the Treatment Phase | 76 Participants |
Secondary
Blood Eosinophil Count (With Consideration of the HES Background Therapy) During Stages 1-3
Mean blood eosinophil counts were summarized over time taking into account the effect of HES background therapy. Eosinophil count observations for only those participants taking mepolizumab in conjunction with prednisone or as monotherapy were included.
Time frame: up to approximately 6 years
Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mepolizumab 750 mg | Blood Eosinophil Count (With Consideration of the HES Background Therapy) During Stages 1-3 | Week 12; n= 69 | 176.4 Cell/uL | Standard Deviation 228.41 |
| Mepolizumab 750 mg | Blood Eosinophil Count (With Consideration of the HES Background Therapy) During Stages 1-3 | Week 24; n= 68 | 272.6 Cell/uL | Standard Deviation 499.78 |
| Mepolizumab 750 mg | Blood Eosinophil Count (With Consideration of the HES Background Therapy) During Stages 1-3 | Week 48; n= 59 | 163.1 Cell/uL | Standard Deviation 146.64 |
| Mepolizumab 750 mg | Blood Eosinophil Count (With Consideration of the HES Background Therapy) During Stages 1-3 | Week 72; n=49 | 237.3 Cell/uL | Standard Deviation 358.36 |
| Mepolizumab 750 mg | Blood Eosinophil Count (With Consideration of the HES Background Therapy) During Stages 1-3 | Week 96; n=43 | 272.8 Cell/uL | Standard Deviation 485.06 |
| Mepolizumab 750 mg | Blood Eosinophil Count (With Consideration of the HES Background Therapy) During Stages 1-3 | Week 168; n=33 | 210.6 Cell/uL | Standard Deviation 283.35 |
| Mepolizumab 750 mg | Blood Eosinophil Count (With Consideration of the HES Background Therapy) During Stages 1-3 | Week 192; n=27 | 208.5 Cell/uL | Standard Deviation 249.01 |
| Mepolizumab 750 mg | Blood Eosinophil Count (With Consideration of the HES Background Therapy) During Stages 1-3 | Week 216; n=23 | 274.8 Cell/uL | Standard Deviation 337.5 |
| Mepolizumab 750 mg | Blood Eosinophil Count (With Consideration of the HES Background Therapy) During Stages 1-3 | Week 240; n=21 | 138.1 Cell/uL | Standard Deviation 138.08 |
| Mepolizumab 750 mg | Blood Eosinophil Count (With Consideration of the HES Background Therapy) During Stages 1-3 | Week 264; n=9 | 466.7 Cell/uL | Standard Deviation 533.99 |
| Mepolizumab 750 mg | Blood Eosinophil Count (With Consideration of the HES Background Therapy) During Stages 1-3 | Week 288; n=2 | 350.0 Cell/uL | Standard Deviation 212.13 |
| Mepolizumab 750 mg | Blood Eosinophil Count (With Consideration of the HES Background Therapy) During Stages 1-3 | MHE100185 Baseline; n=78 | 456.2 Cell/uL | Standard Deviation 713.81 |
| Mepolizumab 750 mg | Blood Eosinophil Count (With Consideration of the HES Background Therapy) During Stages 1-3 | MHE100901 Baseline, n=65 | 467.2 Cell/uL | Standard Deviation 719.66 |
| Mepolizumab 750 mg | Blood Eosinophil Count (With Consideration of the HES Background Therapy) During Stages 1-3 | Week 120; n=40 | 174.3 Cell/uL | Standard Deviation 172.58 |
| Mepolizumab 750 mg | Blood Eosinophil Count (With Consideration of the HES Background Therapy) During Stages 1-3 | Week 144; n=36 | 291.4 Cell/uL | Standard Deviation 546.03 |
Secondary
Change From Baseline in Erythema/Edema Score 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter
The erythema subscale score and edema subscale score are each graded on a 0-3 scale, with 0 = absent , 1 = mild, 2 = moderate, 3 = severe. The total score ranged from 0 to 6, with higher scores indicative of more severe Erythema/Edema. The total score was obtained by summing together the responses for each of the two subscale items. Change from Baseline in erythema/edema total score is the difference between erythema/edema total score at the time point being analyzed to the MHE100901 Baseline score..
Time frame: Baseline and up to approximately 6 years
Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mepolizumab 750 mg | Change From Baseline in Erythema/Edema Score 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 12; n= 59 | 0.0 Scores on a scale | Standard Deviation 1.07 |
| Mepolizumab 750 mg | Change From Baseline in Erythema/Edema Score 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 24; n= 54 | 0.0 Scores on a scale | Standard Deviation 1 |
| Mepolizumab 750 mg | Change From Baseline in Erythema/Edema Score 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 48; n= 36 | 0.0 Scores on a scale | Standard Deviation 1.13 |
| Mepolizumab 750 mg | Change From Baseline in Erythema/Edema Score 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 72; n=38 | 0.2 Scores on a scale | Standard Deviation 0.98 |
| Mepolizumab 750 mg | Change From Baseline in Erythema/Edema Score 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 96; n=21 | -0.1 Scores on a scale | Standard Deviation 1.01 |
| Mepolizumab 750 mg | Change From Baseline in Erythema/Edema Score 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 120; n=11 | -0.2 Scores on a scale | Standard Deviation 0.6 |
| Mepolizumab 750 mg | Change From Baseline in Erythema/Edema Score 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 144; n=9 | -0.2 Scores on a scale | Standard Deviation 0.67 |
| Mepolizumab 750 mg | Change From Baseline in Erythema/Edema Score 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 168; n=6 | 0.5 Scores on a scale | Standard Deviation 1.05 |
| Mepolizumab 750 mg | Change From Baseline in Erythema/Edema Score 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 192; n=4 | 0.8 Scores on a scale | Standard Deviation 0.96 |
| Mepolizumab 750 mg | Change From Baseline in Erythema/Edema Score 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 216; n=4 | 0.3 Scores on a scale | Standard Deviation 1.26 |
| Mepolizumab 750 mg | Change From Baseline in Erythema/Edema Score 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 240; n=11 | 0.3 Scores on a scale | Standard Deviation 0.65 |
| Mepolizumab 750 mg | Change From Baseline in Erythema/Edema Score 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 264; n=8 | 0.0 Scores on a scale | Standard Deviation 0 |
| Mepolizumab 750 mg | Change From Baseline in Erythema/Edema Score 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 288; n=3 | -1.0 Scores on a scale | Standard Deviation 1 |
Secondary
Change From Baseline in QoL and Current Health Status: Mental Summary Score of the SF12 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter
The SF-12v2 is the 12 item abbreviated form of SF-36v2 survey developed by the Medical Outcomes Trust and QualityMetric Incorporated. It provides information about how participants feel, and how well they have been able to perform their usual activities, over the past 4 weeks. SF-12v2 scale questions make up 8 scales: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, Mental Health are for mental component summary. Transformed mental component summary score (MCS-12) is derived using all the 12 items and scored onto a 0-100 scale such that a higher score indicates a better health state and better functioning. Change from Baseline in scale or summary measure score is the difference between the score at the time point being analyzed to Baseline.
Time frame: Baseline and up to approximately 6 years
Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mepolizumab 750 mg | Change From Baseline in QoL and Current Health Status: Mental Summary Score of the SF12 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 12; n= 64 | 2.8 Scores on a scale | Standard Deviation 8.46 |
| Mepolizumab 750 mg | Change From Baseline in QoL and Current Health Status: Mental Summary Score of the SF12 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 36; n= 50 | 1.6 Scores on a scale | Standard Deviation 10.75 |
| Mepolizumab 750 mg | Change From Baseline in QoL and Current Health Status: Mental Summary Score of the SF12 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 60; n=48 | 2.8 Scores on a scale | Standard Deviation 10.34 |
| Mepolizumab 750 mg | Change From Baseline in QoL and Current Health Status: Mental Summary Score of the SF12 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 84; n=47 | 1.5 Scores on a scale | Standard Deviation 8.46 |
| Mepolizumab 750 mg | Change From Baseline in QoL and Current Health Status: Mental Summary Score of the SF12 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 108; n=39 | 2.9 Scores on a scale | Standard Deviation 11.02 |
| Mepolizumab 750 mg | Change From Baseline in QoL and Current Health Status: Mental Summary Score of the SF12 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 132; n=37 | 5.3 Scores on a scale | Standard Deviation 10.2 |
| Mepolizumab 750 mg | Change From Baseline in QoL and Current Health Status: Mental Summary Score of the SF12 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 156; n=41 | 2.1 Scores on a scale | Standard Deviation 10.82 |
| Mepolizumab 750 mg | Change From Baseline in QoL and Current Health Status: Mental Summary Score of the SF12 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 180; n=45 | 2.7 Scores on a scale | Standard Deviation 11.95 |
| Mepolizumab 750 mg | Change From Baseline in QoL and Current Health Status: Mental Summary Score of the SF12 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 204; n=43 | 1.9 Scores on a scale | Standard Deviation 11.54 |
| Mepolizumab 750 mg | Change From Baseline in QoL and Current Health Status: Mental Summary Score of the SF12 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 228; n=44 | 1.8 Scores on a scale | Standard Deviation 11.43 |
| Mepolizumab 750 mg | Change From Baseline in QoL and Current Health Status: Mental Summary Score of the SF12 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 276; n=12 | 3.3 Scores on a scale | Standard Deviation 12.44 |
| Mepolizumab 750 mg | Change From Baseline in QoL and Current Health Status: Mental Summary Score of the SF12 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 252; n=24 | 0.6 Scores on a scale | Standard Deviation 12.13 |
Secondary
Change From Baseline in Quality of Life (QoL) and Current Health Status: Physical Summary Score of the Study Short Form Health Survey (SF-12) 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter
The SF-12v2 is the 12 item abbreviated form of SF-36v2 survey . It provides information about how participants feel, and how well they have been able to perform their usual activities, over the past 4 weeks. SF-12v2 questions make up 8 scales: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, Mental Health . Transformed physical component summary score (PCS-12) is derived using all the 12 items and scored onto a 0-100 scale such that a higher score indicates a better health state and better functioning. Change from Baseline in scale or summary measure score is the difference between the score at the time point being analyzed to Baseline.
Time frame: Baseline and up to approximately 6 years
Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mepolizumab 750 mg | Change From Baseline in Quality of Life (QoL) and Current Health Status: Physical Summary Score of the Study Short Form Health Survey (SF-12) 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 12; n= 64 | -2.0 Scores on the scale | Standard Deviation 8.25 |
| Mepolizumab 750 mg | Change From Baseline in Quality of Life (QoL) and Current Health Status: Physical Summary Score of the Study Short Form Health Survey (SF-12) 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 36; n= 50 | -1.4 Scores on the scale | Standard Deviation 8.76 |
| Mepolizumab 750 mg | Change From Baseline in Quality of Life (QoL) and Current Health Status: Physical Summary Score of the Study Short Form Health Survey (SF-12) 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 60; n=48 | -1.1 Scores on the scale | Standard Deviation 8.91 |
| Mepolizumab 750 mg | Change From Baseline in Quality of Life (QoL) and Current Health Status: Physical Summary Score of the Study Short Form Health Survey (SF-12) 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 84; n=47 | -0.8 Scores on the scale | Standard Deviation 8.43 |
| Mepolizumab 750 mg | Change From Baseline in Quality of Life (QoL) and Current Health Status: Physical Summary Score of the Study Short Form Health Survey (SF-12) 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 108; n=39 | -1.0 Scores on the scale | Standard Deviation 8.23 |
| Mepolizumab 750 mg | Change From Baseline in Quality of Life (QoL) and Current Health Status: Physical Summary Score of the Study Short Form Health Survey (SF-12) 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 132; n=37 | -1.3 Scores on the scale | Standard Deviation 8.33 |
| Mepolizumab 750 mg | Change From Baseline in Quality of Life (QoL) and Current Health Status: Physical Summary Score of the Study Short Form Health Survey (SF-12) 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 156; n=41 | -1.1 Scores on the scale | Standard Deviation 8.66 |
| Mepolizumab 750 mg | Change From Baseline in Quality of Life (QoL) and Current Health Status: Physical Summary Score of the Study Short Form Health Survey (SF-12) 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 180; n=45 | -2.1 Scores on the scale | Standard Deviation 8.1 |
| Mepolizumab 750 mg | Change From Baseline in Quality of Life (QoL) and Current Health Status: Physical Summary Score of the Study Short Form Health Survey (SF-12) 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 204; n=43 | -2.2 Scores on the scale | Standard Deviation 10.02 |
| Mepolizumab 750 mg | Change From Baseline in Quality of Life (QoL) and Current Health Status: Physical Summary Score of the Study Short Form Health Survey (SF-12) 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 228; n=44 | -0.1 Scores on the scale | Standard Deviation 9.41 |
| Mepolizumab 750 mg | Change From Baseline in Quality of Life (QoL) and Current Health Status: Physical Summary Score of the Study Short Form Health Survey (SF-12) 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 252; n=24 | -1.3 Scores on the scale | Standard Deviation 9.6 |
| Mepolizumab 750 mg | Change From Baseline in Quality of Life (QoL) and Current Health Status: Physical Summary Score of the Study Short Form Health Survey (SF-12) 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 276; n=12 | -1.4 Scores on the scale | Standard Deviation 10.76 |
Secondary
Change From Baseline in the Pruritus Visual Analogue Scale (pVAS) 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter
The pruritus visual analogue scale asks participants to rate the status of their Pruritus based on the severity of their itch. Scores range from 0-100 with 0 = No itch and 100 = Worst imaginable itch. Change from Baseline in pVAS score is the difference between the pVAS score at the time point being considered to the MHE100901 Baseline score.
Time frame: Baseline and up to approximately 6 years
Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mepolizumab 750 mg | Change From Baseline in the Pruritus Visual Analogue Scale (pVAS) 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 12; n= 58 | -6.8 Scores on the scale | Standard Deviation 20.01 |
| Mepolizumab 750 mg | Change From Baseline in the Pruritus Visual Analogue Scale (pVAS) 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 24; n= 51 | -4.5 Scores on the scale | Standard Deviation 17.49 |
| Mepolizumab 750 mg | Change From Baseline in the Pruritus Visual Analogue Scale (pVAS) 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 48; n= 46 | -5.1 Scores on the scale | Standard Deviation 26.19 |
| Mepolizumab 750 mg | Change From Baseline in the Pruritus Visual Analogue Scale (pVAS) 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 144; n=32 | -2.8 Scores on the scale | Standard Deviation 18.68 |
| Mepolizumab 750 mg | Change From Baseline in the Pruritus Visual Analogue Scale (pVAS) 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 216; n=21 | -0.8 Scores on the scale | Standard Deviation 13.99 |
| Mepolizumab 750 mg | Change From Baseline in the Pruritus Visual Analogue Scale (pVAS) 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 240; n=17 | 4.4 Scores on the scale | Standard Deviation 12.33 |
| Mepolizumab 750 mg | Change From Baseline in the Pruritus Visual Analogue Scale (pVAS) 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 264; n=7 | 2.7 Scores on the scale | Standard Deviation 13.14 |
| Mepolizumab 750 mg | Change From Baseline in the Pruritus Visual Analogue Scale (pVAS) 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 288; n=2 | 39.5 Scores on the scale | Standard Deviation 54.45 |
| Mepolizumab 750 mg | Change From Baseline in the Pruritus Visual Analogue Scale (pVAS) 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 72; n=39 | -0.1 Scores on the scale | Standard Deviation 20.77 |
| Mepolizumab 750 mg | Change From Baseline in the Pruritus Visual Analogue Scale (pVAS) 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 96; n=41 | 1.0 Scores on the scale | Standard Deviation 27.63 |
| Mepolizumab 750 mg | Change From Baseline in the Pruritus Visual Analogue Scale (pVAS) 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 120; n=38 | -0.3 Scores on the scale | Standard Deviation 17.84 |
| Mepolizumab 750 mg | Change From Baseline in the Pruritus Visual Analogue Scale (pVAS) 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 168; n=33 | -4.9 Scores on the scale | Standard Deviation 26.55 |
| Mepolizumab 750 mg | Change From Baseline in the Pruritus Visual Analogue Scale (pVAS) 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter | Week 192; n=30 | -1.2 Scores on the scale | Standard Deviation 21.54 |
Secondary
For Those Participants Who Completed 9 Months of Dosing in Study MHE100185 and Achieved a Prednisone Level <=10 mg: Number of Participants Achieving <= 10 mg Prednisone (as Sole Background Therapy) for >= 3months
Participants from study MHE100185 who completed the 9 months treatment period and achieved a level of \<=10 mg of prednisone at study end were analyzed. Duration of doses \<=10 mg was determined by examining changes in the prednisone dosing or allowable alternative corticosteroid medication (prednisone equivalents). Start and stop dates of other HES medications were checked to ensure that they did not overlap with the steroid dosing dates. If it did, then the number of days \<=10 mg during this overlap was considered as zero and the cumulative days reset to zero, as the endpoint was assessing prednisone dose as sole background therapy. The dosing criteria for this endpoint was considered as achieved if the duration of dosing was minimum of 84 days (3months).
Time frame: up to approximately 6 years
Population: ITT Population. Only those participants who completed 9 months of dosing in study MHE100185 and achieved a prednisone level \<=10 mg were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mepolizumab 750 mg | For Those Participants Who Completed 9 Months of Dosing in Study MHE100185 and Achieved a Prednisone Level <=10 mg: Number of Participants Achieving <= 10 mg Prednisone (as Sole Background Therapy) for >= 3months | 39 Participants |
Secondary
For Those Participants Who Completed 9 Months of Dosing in Study MHE100185 and Achieved a Prednisone Level >10 mg: Number of Participants Achieving <=10 mg Prednisone (as Sole Background Therapy) for >= 8 Weeks
Participants from study MHE100185 who completed the 9 months treatment period and achieved a level of prednisone of \>10 mg at the end of the study were analyzed. Duration of doses \<= 10 mg were determined by examining changes in the prednisone dosing or allowable alternative corticosteroid medication (prednisone equivalents). Start and stop dates of other HES medications were checked to ensure that they did not overlap with the steroid dosing dates. If overap occurred, then the number of days \<=10 mg during this overlap was considered as zero and the cumulative days reset to zero, as the endpoint was assessing prednisone dose as sole background therapy. The dosing criteria for this endpoint was considered as achieved if the duration of dosing was minimum of 53 days (8 weeks).
Time frame: up to approximately 6 years
Population: ITT Population. Only those participants who completed 9 months of dosing in study MHE100185 and achieved a prednisone level \>10 mg were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mepolizumab 750 mg | For Those Participants Who Completed 9 Months of Dosing in Study MHE100185 and Achieved a Prednisone Level >10 mg: Number of Participants Achieving <=10 mg Prednisone (as Sole Background Therapy) for >= 8 Weeks | 5 Participants |
Secondary
For Those Participants Who Entered Stage 1 From Study MHE100185 With >10 mg Prednisone: Number of Participants Achieving a Prednisone Dose <=10 mg (as Sole Background Therapy) for>=3 Months
Participants from study MHE100185 who completed the 9 months treatment period and achieved a level of \>10 mg prednisone at the end of the study and participants who withdrew from the study early who were at a prednisone dose level \>10 mg were analyzed. Duration of doses \<= 10 mg was determined by examining changes in the prednisone dosing or allowable alternative corticosteroid medication (prednisone equivalents). Start and stop dates of other HES medications were checked to ensure that they do not overlap with the steroid dosing dates. If it did, then the number of days \<=10 mg during this overlap was considered as zero and the cumulative days reset to zero, as the endpoint was assessing prednisone dose as sole background therapy. The dosing criteria for this endpoint was considered as achieved if the duration of dosing was minimum of 84 days (3months)
Time frame: up to approximately 6 years
Population: ITT Population. Only those participants who entered Stage 1 from study MHE100185 with \>10 mg prednisone were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mepolizumab 750 mg | For Those Participants Who Entered Stage 1 From Study MHE100185 With >10 mg Prednisone: Number of Participants Achieving a Prednisone Dose <=10 mg (as Sole Background Therapy) for>=3 Months | 22 Participants |
Secondary
For Those Participants Who Entered Stage 2 From Study MHE100185 With a Prednisone Level of <=10 mg Prednisone: Number of Participants Achieving a Prednisone Dose <=10 mg (as Sole Background Therapy) for >=3 Months;
Participants from study MHE100185 who completed the 9 months treatment period and achieved a level of \<=10 mg of prednisone at study end and participants who withdrew from the study early who were at a prednisone dose level \<=10 mg were analyzed. Duration of doses \<= 10 mg were determined by examining changes in the prednisone dosing or allowable alternative corticosteroid medication (prednisone equivalents). Start and stop dates of other HES medications were checked to ensure that they did not overlap with the steroid dosing dates. If overlap occurred, then the number of days \<=10 mg during this overlap was considered as zero and the cumulative days reset to zero, as the endpoint was assessing prednisone dose as sole background therapy. The dosing criteria for this endpoint was considered as achieved if the duration of dosing was minimum of 84 days (3months).
Time frame: up to approximately 6 years
Population: ITT Population. Only those participants who entered Stage 2 from study MHE100185 with a prednisone level of \<=10 mg prednisone were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mepolizumab 750 mg | For Those Participants Who Entered Stage 2 From Study MHE100185 With a Prednisone Level of <=10 mg Prednisone: Number of Participants Achieving a Prednisone Dose <=10 mg (as Sole Background Therapy) for >=3 Months; | 43 Participants |
Secondary
Number of Participants Achieving an Eosinophil Level of < 600 Cell/Microliter (uL) (in Addition to the Lowest Background Therapy) at the End of Study
The criteria for eosinophil count was achieved if the participant's eosinophil count remained below \<600 cell/uL for the last observation on study i.e. within length of dosing cycle + 7 days of last dose of study drug. For participants who entered in Stage 1, HES medications taking prior to the first infusion date in Stage 2 were considered as the lowest background therapy. For participants who entered in Stage 2, HES medications taken on the date that immediately preceded the first infusion date of study drug and had not been discontinued was regarded as the lowest background therapy. If the dose of the lowest background therapy had increased or the medication had changed or the participant had not reached their lowest background therapy, the participant was regarded as not achieving this endpoint.
Time frame: up to approximately 6 years
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mepolizumab 750 mg | Number of Participants Achieving an Eosinophil Level of < 600 Cell/Microliter (uL) (in Addition to the Lowest Background Therapy) at the End of Study | 46 Participants |
Secondary
Number of Participants Achieving a Prednisone Level of =<10 mg (as Sole Background Therapy) at the End of Study
Participants who were receiving a prednisone dose level of =\<10 mg as their sole background therapy at the end of the study were included for the analysis.
Time frame: up to approximately 6 years
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mepolizumab 750 mg | Number of Participants Achieving a Prednisone Level of =<10 mg (as Sole Background Therapy) at the End of Study | 62 Participants |
Secondary
Number of Participants by Dosing Frequency Groups (Defined as Two Week Dosing Ranges Greater Than a 4 Week Interval) at the End of Stage 2
The number of participants at the end of Stage 2 with study medication dosing frequencies of 4 weeks, 5-6 weeks, 7-8 weeks, 9-10 weeks, 11-12 weeks, 13-16 weeks, 17-20 weeks, 21-24 weeks and \>24 weeks were summarized. The first infusion date in Stage 3 and the last infusion date in Stage 2 were used to calculate the dosing frequency.
Time frame: up to approximately 6 years
Population: ITT Population. Only those participants available at end of Stage 2 were included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mepolizumab 750 mg | Number of Participants by Dosing Frequency Groups (Defined as Two Week Dosing Ranges Greater Than a 4 Week Interval) at the End of Stage 2 | <4 Weeks | 1 Participants |
| Mepolizumab 750 mg | Number of Participants by Dosing Frequency Groups (Defined as Two Week Dosing Ranges Greater Than a 4 Week Interval) at the End of Stage 2 | 4 Weeks | 5 Participants |
| Mepolizumab 750 mg | Number of Participants by Dosing Frequency Groups (Defined as Two Week Dosing Ranges Greater Than a 4 Week Interval) at the End of Stage 2 | 5 to 6 Weeks | 6 Participants |
| Mepolizumab 750 mg | Number of Participants by Dosing Frequency Groups (Defined as Two Week Dosing Ranges Greater Than a 4 Week Interval) at the End of Stage 2 | 7 to 8 Weeks | 4 Participants |
| Mepolizumab 750 mg | Number of Participants by Dosing Frequency Groups (Defined as Two Week Dosing Ranges Greater Than a 4 Week Interval) at the End of Stage 2 | 9 to 10 Weeks | 5 Participants |
| Mepolizumab 750 mg | Number of Participants by Dosing Frequency Groups (Defined as Two Week Dosing Ranges Greater Than a 4 Week Interval) at the End of Stage 2 | 11 to 12 Weeks | 8 Participants |
| Mepolizumab 750 mg | Number of Participants by Dosing Frequency Groups (Defined as Two Week Dosing Ranges Greater Than a 4 Week Interval) at the End of Stage 2 | 13 to 16 Weeks | 12 Participants |
| Mepolizumab 750 mg | Number of Participants by Dosing Frequency Groups (Defined as Two Week Dosing Ranges Greater Than a 4 Week Interval) at the End of Stage 2 | 21 to 24 Weeks | 4 Participants |
| Mepolizumab 750 mg | Number of Participants by Dosing Frequency Groups (Defined as Two Week Dosing Ranges Greater Than a 4 Week Interval) at the End of Stage 2 | >24 Weeks | 6 Participants |
| Mepolizumab 750 mg | Number of Participants by Dosing Frequency Groups (Defined as Two Week Dosing Ranges Greater Than a 4 Week Interval) at the End of Stage 2 | 17 to 20 Weeks | 8 Participants |